Walker

Bruce Walker, MD

Lab Info:

Principal Investigator: Bruce Walker, MD

Lab Staff: 6 post doctoral fellows

Office/Location: 400TS 870

Phone: (857) 268-7072

Email: bwalker@partners.org | Assistant: Kristina Bradford kebradford@partners.org

Category: Members

The Walker laboratory focuses on mechanisms of immune control in HIV infection, focusing in particular on persons who control HIV infection spontaneously without the need for medication. Through an international collaboration now funded by the Gates Foundation, more than 1500 persons who control HIV infection to less than 2000 RNA Copies/ml without the need for antiviral medications have been recruited, and immunologic, virologic and host genetic mechanisms accounting for this remarkable phenotype are being investigated. Our results,  published in Science, indicate that the major genetic determinants of HIV control affect the nature of the peptide-HLA binding. We are currently focusing our research efforts on this interaction and how it impacts the inductive and effector phases of the CD8 T cell response.

 

Other projects currently underway are building on a observation that the antiviral efficacy of CTL varies dramatically among different epitopes and different restricting HLA alleles, in an attempt to define the major antiviral effector functions and apply these to vaccine development. At the same time, efforts are underway to define the subset of CD8 T cell responses that exert the strongest antiviral effect, and to define those responses that are simply passengers and fail to contribute to immune control.

 

In addition to these efforts in Boston, a major effort is underway at our laboratory at the Nelson Mandela School of Medicine at the University of KwaZulu-Natal, South Africa, where a major population based effort is underway to define evolution of clade C virus infection under immune selection pressure, and to define predictable pathways to immune escape. We have established a mechanism for recruitment of persons with acute HIV infection by screening persons who test antibody negative at VCT (now HCT) sites in KZN. We anticipate an expanding collaboration with persons at the Ithembalebantu Clinic in Umlazi to accelerate these studies, which will include examination of tissue biopsies.

 

Persons interested in joining this lab should have a strong background in immunology and/or molecular biology, a strong interest in working on immune responses in humans, and an ability to work relatively independently. The lab is highly collaborative with other labs within the Ragon Institute and outside, and thus seeks people who are committed to scientific collaboration. Please visit the Training Programs page for information about how to apply.

 

Links

Acute HIV Infection Research Program

International HIV Controllers Study

Harvard Center for AIDS Research (CFAR)

Howard Hughes Medical Institute

 

Important Accomplishments

  • Identification of strong circulating HIV-specific cytotoxic T lymphocytes in infected persons.
  • Identification of HIV-specific CD4 T cells and their association with immune control of HIV.
  • Identification of immunoregulatory pathways that turn HIV-specific immune responses off in vivo.
  • Demonstration of the superior antiviral efficacy of Gag-specific CD8 T cell responses.

Present Areas of Investigation


  • Define the relative antiviral efficacy of epitope-specific CTL responses in infected persons
  • Define the predicatable pathways to immune escape in infected persons
  • Define the mechanisms that underlie effective cell killing
  • Define the mechanisms of spontaneous control of HIV infection using a genome wide association scan.


Selected Recent Publications


1.     Day CL, Kaufmann DE, Kiepiela P, Brown JA, Moodley ES, Reddy S, Mackey EW, Miller JD, Leslie AJ, DePierres C, Mncube Z, Duraiswamy J, Zhu B, Eichbaum Q, Altfeld M, Wherry EJ, Coovadia HM, Goulder PJ, Klenerman P, Ahmed R, Freeman GJ, Walker BD. 2006. PD-1 expression on HIV-specific T cells is associated with T-cell exhaustion and disease progression. Nature 443: 350-4

 
2.     Kaufmann DE, Kavanagh DG, Pereyra F, Zaunders JJ, Mackey EW, Miura T, Palmer S, Brockman M, Rathod A, Piechocka-Trocha A, Baker B, Zhu B, Le Gall S, Waring MT, Ahern R, Moss K, Kelleher AD, Coffin JM, Freeman GJ, Rosenberg ES, Walker BD. 2007. Upregulation of CTLA-4 by HIV-specific CD4+ T cells correlates with disease progression and defines a reversible immune dysfunction. Nat Immunol 8: 1246-54

 
3.     Chen H, Piechocka-Trocha A, Miura T, Brockman MA, Julg BD, Baker BM, Rothchild AC, Block BL, Schneidewind A, Koibuchi T, Pereyra F, Allen TM, Walker BD. 2009. Differential neutralization of human immunodeficiency virus (HIV) replication in autologous CD4 T cells by HIV-specific cytotoxic T lymphocytes. J Virol 83: 3138-49

 
4.     Miura T, Brockman MA, Brumme ZL, Brumme CJ, Pereyra F, Trocha A, Block BL, Schneidewind A, Allen TM, Heckerman D, Walker BD. 2009. HLA-associated alterations in replication capacity of chimeric NL4-3 viruses carrying gag-protease from elite controllers of human immunodeficiency virus type 1. J Virol 83: 140-9

 
5.     Kosmrlj A, Read EL, Qi Y, Allen TM, Altfeld M, Deeks SG, Pereyra F, Carrington M, Walker BD, Chakraborty AK. 2010. Effects of thymic selection of the T-cell repertoire on HLA class[thinsp]I-associated control of HIV infection. Nature 465: 350-4

 
6.     The International HIV Controller Study. 2010. The major genetic determinants of HIV control affect HLA class I peptide binding. Science in press


 

Laboratory Staff

kristina
Kristina Bradford | kebradford@partners.org
Kristina has been the Executive Assistant to Bruce D. Walker since October 2010 and helps to coordinate the Walker Lab in addition to the Ragon Steering Committee. Currently obtaining a Masters Degree in Ethics and Public Policy, Kristina hopes to continue her work in international health policy and end human trafficking once the role of T-cell help in controlling HIV infection is determined by the Walker Lab. She loves to travel and jumps at every chance to work with the Ragon Institute programs in South Africa.
alex
Alexander Carchidi | acarchidi@partners.org
Alex is a research technician in the processing lab. He graduated from Boston University in 2011 with majors in biology and philosophy. His capstone project at BU was a detailed action plan to contain the problem of drug resistant tuberculosis in South Africa. Alex’s philosophy thesis project focused on the philosophy of physics and argued for the Copenhagen interpretation of quantum physics against the many worlds theory. He is from Sherborn, MA, and enjoys looking at strange insects and animals, eating, surrealist humor, and electronic music.
huabio
Huabiao Chen | hchen13@partners.org
Huabiao is a Senior Research Scientist at Ragon Institute. He joined Walker lab in 2005 as a postdoctoral fellow. He is interested in understanding T cell responses by which some remarkable HIV-1-infected individuals are able to persistently control HIV-1 replication without medications (named elite controllers). He currently focuses his efforts on investigation of TCR usages modulating antiviral efficacy of cytotoxic T cells and characterization of the structural basis of TCR signal transduction and CTL antiviral function. Before he moved to USA he had been conducting research in China for 12 years, specializing in understanding immune mechanisms and developing new diagnostics tools and prevention strategies for a wide range of infectious diseases.
oliver
Oliver Davis | odavis1@partners.org
Oliver began working at the Ragon Institute in 2011, and has been working as a technician in the Walker lab since 2012. He graduated from Amherst College in 2011, where he majored in chemistry. In the Walker lab Oliver has been working on a project to that seeks to understand how the antiviral activity of different CD4 T cell subsets can be harnessed to make an effective HIV vaccine. Outside of his work at the Ragon, Oliver’s scientific interests include the molecular basis for human disease and pharmaceutical development. In his spare time he also enjoys hiking, camping, snowboarding, and building and riding bicycles.
justin
Justin Fang | jfang@partners.org
Justin Fang is a research technologist working under Huabiao Chen for the Bruce Walker lab. He received his bachelor of science in Biology from the University of Massachusetts at Amherst in 2008. While working for Huabiao Chen, his main focus of work involve T-Cell receptor sequencing and how these various clonotypes may contribute to protection. He is from Malden, Massachusetts and while not doing science, he enjoys playing sports, trying new foods, listening to music, and traveling around the world.
guarav Gaurav Gaiha
I am originally from Chicago, IL. I completed by BS in Biochemistry and BA in Economics from the University of Illinois in 2003. I subsequently obtained a PhD in Biochemistry with a focus in HIV immunology at Oxford University working in the MRC Immunochemistry Unit and in collaboration with the MRC Human Immunology Unit. After Oxford, I moved onto the Health Sciences and Technology (HST) program at Harvard Medical School to complete my MD, which I completed with Magna Cum Laude honors based on work I completed at the Ragon Institute of MGH, MIT and Harvard in the lab of Prof. Bruce Walker. I am now a 2nd-year Internal Medicine Resident at Massachusetts General Hospital and continue to pursue active projects in the lab.My research interests are focused on understanding the properties that define successful and dysfunctional HIV-specific CD8+ T cell responses in patients with divergent clinical outcomes using transcriptional profiling and shRNA knockdown technology. I am also working on a novel network analysis platform to identify critical areas of mutational constraint within the HIV proteome and ultimately hope to parlay this work into novel T-cell based vaccine designs.”
sophia
Sophia Geffen | sgeffen@partners.org
Sophia joined the Walker Lab as a technician in August 2013 after spending the summer in Kenya interning with UNAIDS and the Pan-African Positive Women’s Coalition. She received her BA in Public Policy Analysis/Global Health from Pomona College in May 2013. She hopes to pursue medicine and eventually contribute to global health policymaking.
brad
Brad Jones | rbjones@partners.org
Brad Jones is currently a Banting Fellow at the Ragon Institute and a holder of an OHTN Junior Investigator Development Award. He received his Ph.D. degree from the University of Toronto, working with Dr. Mario Ostrowski. His previous contributions include the identification of a novel mechanism by which HIV infection drives immune cell dysfunction (Tim-3), and the exploration of human endogenous retroviruses as novel targets for HIV vaccines. Currently, Brad is working with Drs. Bruce Walker and Darrell Irvine on harnessing a technology developed at MIT to enhance the ability of immune cells (T-cells) to detect and kill latently HIV infected cells. Latently-infected cells persist in antiretroviral treated individuals by hiding from the natural immune response and thus present a barrier to eradicating infection. The ultimate goal of this work is to develop a therapeutic approach to flush this viral reservoir and thus achieve sterilizing cures of HIV. In his free time Brad enjoys hiking and camping with his dog.
dan
Dan Karel | dkarel@partners.org
Dan joined the Walker lab as a Research Technician in August of 2011. He completed his undergraduate degree in Biology with a minor concentration in Environmental Analysis and Policy at Boston University, class of 2011. Hailing from Westchester County in New York, he has a passion for science and learning, live music, the great outdoors and traveling the world. Dan aspires to be a primary care physician.
katja
Katja Kleinsteuber | kkleinsteuber@partners.org
Katja is a postdoctoral fellow in the Walker lab working on CD8+ T cell responsesduring HIV infection. She joined the lab in February 2013 and is interested in human immune responses to infectious diseases. She is a passionate user of the CyTOF at the Ragon Institute. She received her Masters degree in Biochemistry and Molecular Biology from the University of Hamburg (Germany) and worked at the Bernhard-Nocht-Institute for Tropical Medicine in Hamburg for her PhD studies about human CD4+ T cell regulation in the context of tuberculosis.
orestOrestes Mavrothalassitis | omavrothalassitis@partners.org
Orestes is a research technician in the Walker Lab. He joined the lab in June 2013 after graduating with a BS degree in Molecular and Cellular Biology from the Johns Hopkins University. Originally from Frederick, Maryland, Orestes enjoys playing soccer, applying to medical school, eating unreasonable amounts of food, and speaking Greek to anybody who will listen.
pedro
Pedro Lamothe Molina | plamothemolina@partners.org
Pedro is a Ph.D. student in Biological Sciences in Public Health from Harvard University. He joined the Walker Lab in February 2013 to study the CD8+ T cells immune responses against HIV infection. Pedro is originally from Mexico City where he did his undergraduate studies in Electronic Engineering and where he later received his Medical degree. He wanted to do more basic science research, so he did his M.S. in Biotechnology at Johns Hopkins University. He spends the time he is outside the lab, cycling and training for Ironman triathlons. He loves his Fox Terrier dog named Simon but the winter in Massachusetts… well, not so much.
blandine
Blandine Monel | blandine_monel@dfci.harvard.edu
Blandine Monel is a Research Fellow at the Ragon Institute and her research is focused on phenotyping the CD8+ T cells and studying their functionality in HIV + patients. She obtained her Master in Pharmacology Engineering at the Ecole Polytechnic of the University of Nice in France. During her Master she has studied the HIV Integrase at the Dana Farber Cancer Institute in Boston. She got her Ph.D. from the University Paris-Diderot ( France) and HIV cell-to-cell transmission in lymphocytes CD4+Tcells . In January 2013 she joined Walker lab as a postdoctoral fellow. Besides love for science she enjoys playing piano and volleyball.
stephanie
Stefanie Mueller | smueller4@mgh.harvard.edu
Stefanie Mueller joined the labs of Drs. Darrell Irvine and Bruce Walker as Research Technician in April 2013. After graduating from the Medical Technical Academy Esslingen (Germany) in 2003 she collected experience in different Research Labs at the University of Tuebingen. Among others in the Department of Anesthesiology and Intensive Care Medicine where she worked on understanding the “Role of Adenosine Receptors for PMN migration into the lung during ARDS”, as well as in the Department of Dermatology with the main focus on effective tumor defense through mast cells. When she is not in the lab she enjoys traveling, music and art.
rachel
Rachel O’Connor | rconnor1@partners.org
Rachel graduated from Syracuse University with a Bachelor of Science in Biology. After college, she returned to Boston in August 2012 to become an invaluable member of the Walker lab. Rachel is the current world-record holder for number of T-cell clones generated in 6 months, and her tremendous work ethic is a source of inspiration for her colleagues. When she is not in lab she enjoys trying to cook and traveling.
ryan_park
Ryan Park | rjpark@partners.org
Ryan is an MD student at Harvard Medical School. He received a B.S. and an M.S. in Molecular Biophysics and Biochemistry from Yale University in 2012. He is in the Harvard-MIT Health Sciences & Technology (HST) program and joined the Walker lab in January 2013 for his thesis project. He’s originally from Los Angeles but has also lived in Chicago, Fort Worth, and Seoul. In the lab, he is trying to understand the mechanism for the differential function of CD8+ T cell clones from Elite Controllers and Chronic Progressors. In his dwindling time outside of the lab and classroom, he enjoys cooking, playing the saxophone, and reading and dreaming about fast cars.
alicja
Alicja Piechocka-Trocha | atrocha@partners.org
Alicja is a Senior Laboratory Manager for the Ragon Institute and has been working for Dr. Bruce Walker for the last 24 years. Trained as a veterinarian from Polish Agriculture University in Olsztyn, she began to perform research, and despite all odds, she truly learned to love it. The aspect of teaching and educating future aspiring scientist as well as cultivating all habits of safe and meticulous lab work in young students and fellows has become a professional journey for her. What they learn with Alicja they will apply in their new endeavors. When not at work she enjoys reading books, long nature walks and skiing.
srin
Srinika Ranasinghe | sranasinghe@partners.org
Srinika is a Research Fellow at the Ragon Institute working on HIV-specific CD4 T cell responses in natural HIV infection and vaccination strategies. She received her B.A/M.Ain Biological Sciences, and obtained her PhD in HIV immunology under the mentorship of Prof. Sir Andrew McMichael, at the University of Oxford. In 2010, she was delighted to join the Ragon Institute, where her research has focused on identifying epitope-specific CD4 T cell responses and their HLA class II restriction. She is also a young investigator in the Walker and Kaufmann research foci of CHAVI-ID, which seeks to understand the pivotal role of CD4 T follicular helper cells in generating broadly neutralizing antibodies against HIV. Srinika loves exploring the restaurants of Boston and kayaking on the Charles River.
damien2
Damien Soghoian | dsoghoian@partners.org
Damien Soghoian is a PhD student in Program in Virology at Harvard University. He received his B.S. in Biology from Caltech and worked at Caltech as a technician and teaching assistant until beginning his PhD. In the Walker lab and as part of the CHAVI-ID group at the Ragon Institute, Damien studies HIV-specific CD4 T cell responses, particularly cytolytic CD4 T cell responses–those CD4 T cells that have the unique ability to kill. His hobbies include flow cytometry and searching for a real hobby.
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